The Path to a COVID-19 Vaccine: Large-Scale Efficacy Testing Has Begun

By the bioMérieux Connection Editors

As of June 30, 2020, three vaccine candidates for COVID-19 are in large-scale efficacy testing, or Phase III clinical trials. During this phase, the vaccine is given to thousands of volunteers to see if it protects them from becoming infected with the virus, and their results are compared to those who are given a placebo (a substance, such as a sugar pill or saline solution, that has no effect and is used as a control in testing). The farthest-along candidates are a viral vector vaccine being tested by the University of Oxford and AstraZeneca, a repurposed vaccine, originally developed in the early 1900s for protection against tuberculosis, and a whole-virus vaccine being tested by the state-owned Chinese company Sinopharm.

Viral vector vaccines are vaccines that use a virus to deliver particular genes into cells to provoke an immune response. The vaccine created to protect against smallpox, which led to the eradication of the disease in 1978, was a viral vector vaccine. AstraZeneca announced in mid-June that they had reached an agreement with Europe’s Inclusive Vaccine Alliance to supply 400 million doses to the European countries that wish to participate in the initiative. The company’s CEO, Pascal Soriot, also announced they are in talks with Japan, Russia, Brazil, and China about supplying the vaccine if it is approved.

The repurposed vaccine in a Phase III trial is being tested by Murdoch Children’s Research Institute in Australia. This vaccine is being tested to see if it partially protects against the coronavirus. It is not acknowledged by the World Health Organization as one of the candidate coronavirus vaccines in clinical evaluation, but it has been reported that several other trials investigating it are also underway.

A whole virus vaccine is a vaccine that uses a weakened or inactive version of a virus to provoke an immune response. The annual flu shot is typically this type of vaccine. Sinopharm’s Phase III trial will be conducted in the United Arab Emirates due to few confirmed COVID-19 cases in China.

COVID-19 Vaccine Candidates Using New Technology

Some of the cutting-edge technology being used to create a coronavirus vaccine also appears promising so far. One of the front-runners is Moderna’s vaccine candidate that is in a Phase II trial and uses messenger RNA (mRNA) that carries genetic code for part of the coronavirus’s spike protein. This is the portion of the virus that allows it to attach to human cells and invade them. When that portion of the spike protein’s mRNA is given to a healthy person, it may lead their cells to manufacture the viral protein. At the same time, there is no risk for COVID-19 infection, because the body’s cells are not replicating the virus—they are only replicating one portion of the protein. The presence of the viral protein can then alert the person’s immune system, stimulating it to create antibodies. This process is known as genetic immunization, and no vaccine with this technology has yet reached the market, in part because mRNA is structurally fragile and can break apart before it makes it to the body’s cells.

The Clinical Trial Process for Vaccine Candidates

Clinical trials are a vital part of clinical research at the heart of all medical advances. They look at new ways to prevent, detect, or treat disease and can generally take several years to complete. Often, clinical trials begin with a preclinical phase; during this phase the product under investigation is not yet tested on humans. For example, vaccine candidates may first be tested on animals such as mice or monkeys to see if they produce an immune response. Once the product appears to work as it should, scientists can move forward with Phase I.

Most of the time, a clinical trial contains four phases, and three of them occur before the approval stage. During Phase I, the new product is tested on a small number of volunteers. This phase tests the product’s safety and can help researchers determine crucial aspects of the product’s use, such as dosage. During Phase II, the product is tested on hundreds of volunteers. These volunteers are often split into groups, such as children and adults, to see if the product works differently for each group. During Phase III, the product is given to thousands of volunteers. These results are often compared to the results of those who received a placebo.

The next stage is the approval stage, followed by Phase IV. Regulators in each country can review clinical trial results and determine if the product is approved. The pandemic may lead to a vaccine being approved through Emergency Use Authorization (EUA). The EUA authority allows the FDA to help strengthen the nation’s public health by facilitating the availability of medical countermeasures (MCMs) needed during public health emergencies. If a vaccine is approved by the FDA and made available to the public, researchers track its safety in the general population, seeking more information about its benefits and optimal use. This is considered Phase IV of a clinical trial.

Manufacturing COVID-19 Vaccines

If a vaccine is approved, it will need to be mass-produced so that it can be widely available. Drug manufacturers generally have the most experience mass-producing inactivated vaccines, made with killed viruses (a type of viral vector or whole-virus vaccine), so this kind may be the easiest to produce in large quantities. Manufacturing a vaccine is profoundly complex, and no company has ever manufactured millions of dosages of vaccines that use mRNA technology, such as Moderna’s. Despite what has or has not been done before, private companies are forming partnerships, such as Moderna’s partnership with Swiss contract drug maker Lonza, to have a plan for manufacturing and distribution if their vaccine is approved. The US federal government has also taken action with the creation of Operation Warp Speed.

Operation Warp Speed aims to match the vaccine development process with the development of manufacturing infrastructure and logistics. The goal is that vaccines will be able to be mass-produced as soon as they are approved. The US government has selected five companies as the most likely candidates to produce a COVID-19 vaccine to be a part of the operation.

The Importance of Vaccination

Many diseases that used to be prevalent in the U.S. no longer are, thanks to vaccines. The COVID-19 outbreak can serve as a reminder of the value that vaccines provide us. Without vaccines, many more diseases would regularly ravage communities around the world. The availability of a safe and effective vaccine for COVID-19 is well-recognized as a key tool to contribute to the control of the pandemic.

Opinions in this article are not necessarily those of bioMérieux, Inc.

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